MHC (major histocompatibility complex) is a gene complex related to graft rejection. A human MHC is referred to as HLA (Human Leukocyte A system). Rich polymorphism is an essential feature of the HLA gene system. There are a variety of variants, in human populations, of the DNA sequences in many gene loci in the HLA complex, which variants are called alleles. The HLA allele system is located at the sixth chromosome. Since human is a randomly mating heterozygous population, the probability that two HLA alleles are completely the same is little for each individual, not only making HLA be a system with most abundant polymorphism in human body, but also making the HLA allele and a product thereof in each individual be a biological “identity card” for the uniqueness possessed by this individual, i.e., a marker of an individuality. The polymorphism of the HLA system ensures suitable immune responses of the population to various pathogens such that the continuation of the population is guaranteed and the stability thereof is maintained. Many HLA molecules have been found to be associated with drug reactions in different populations. For example, the HLA-B*1502 alleles in Chinese population and Thai population, or the HLA-A*3101 alleles in Caucasian population and Japanese population are related to drug hypersensitivity reactions resulted from Carbamazepine; the HLA-B*5701 alleles in Caucasian population are related to drug reactions resulted from Abacavir; the HLA-B*5801 alleles in Chinese population are related to drug reactions resulted from Allopurinol. No drug reaction is found to be attributed to the HLA-B*1301 allele up to now, however, it is previously reported that this locus was related to allergic dermatitis resulted from trichloroethylene (an industrial solvent) (Li H, Dai Y, Huang H, et al. HLA-B*1301 as a biomarker for genetic susceptibility to hypersensitivity dermatitis induced by trichloroethylene among workers in China. Environ Health Perspect 2007; 115:1553-6).
Dapsone (4,4′-diamino diphenyl sulfone, DDS), synthesized in 1908, is anti-infective and anti-inflammatory. This drug, alone or in combination with other drugs, may be widely used in the treatment of infectious diseases (such as leprosy, malaria, diseases induced by Actinomyces infection, and pneumocystis carinii pneumonia due to HIV infection), or in the treatment of chronic inflammatory diseases characterized in abnormal infiltration of neutrophils or eosinophils (such as autoimmune bullous disease, persistent uplift erythema, pustular psoriasis, pyoderma gangrenosum, acne). In addition, this drug may further serve to treat rheumatic arthritis, and at the same time protect, in a certain degree, the nerves of the patient with acute ischemic stroke.
Previous epidemiological studies showed that about 0.5-3% of the patients receiving DDS treatment may suffer from drug hypersensitivity syndrome, with a mortality rate of about 11-13%. As early as 1949, Lowe noticed this phenomenon; and this disease was formally designated as “dapsone hypersensitivity syndrome” (DHS) in 1951. DHS, a serious heterogeneous reaction of an individual to a drug, often occurs within 4-6 weeks after the DDS treatment, with the clinical manifestations including high fever, rash, and visceral involvement (typically liver and blood system involvement), and even organ failure in severe condition. With DDS employed worldwide in combined chemotherapy of leprosy and chemoprevention of pneumocystis carinii pneumonia due to HIV infection, the incidence of DHS is increased dramatically. A recent systematic review for a published epidemiological article summarizes that the prevalence rate of DHS is about 1.4%. However, there is no reliable detection method available for predicting the risk of DHS by now.